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By the middle of 2021, we are still immersed in the coronavirus disease 2019 (COVID-19) pandemic, caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). The concurrence of this new pandemic in regions where human immunodeficiency virus (HIV) and tuberculosis (TB) infections possess the same epidemiological consideration, has arisen concerns about the prognosis, clinical management, symptomatology, and treatment of patients with triple infection. At the same time, healthcare services previously devoted to diagnosis and treatment of TB and HIV are being jeopardized by the urgent need of resources and attention for COVID-19 patients. The aim of this review was to collect any article considering the three conditions (HIV, TB, and SARS-CoV-2), included in PubMed/Medline and published in the English language since the beginning of the COVID-19 pandemic. We focused on detailed descriptions of the unusual cases describing the three co-infections. Eighty-four out of 184 publications retrieved met our inclusion criteria, but only three of them reported cases (five in total) with the three concomitant infections. The clinical evolution, management, and therapy of all of them were not different from mild/severe cases with exclusive COVID-19; the outcome was not worse either, with recovery for the five patients. Cases of patients with COVID-19 besides HIV and TB infections are scarce in literature, but studies deliberately embracing the triple infection as a priori inclusion criterion should be carried out in order to provide a complete understanding of joint influence.

The presence of transmission clusters (TCs) and their epidemiological characteristics in a treatment-naive cohort of HIV-1 patients in southern Spain over a decade (2004-2015) were evaluated. Protease and reverse transcriptase sequences provided by each genotype test were used in the phylogenetic study, performed first by the neighbor-joining method and then confirmed by Bayesian analysis. We collected clinical, immunovirological, and demographic data for all patients included. Our cohort comprised 757 patients, 428 (56.5%) belonging to a TC. Overall, we found 123 TCs, 21 of them comprising five or more individuals and three with ≥10 sequences. Forty-three TCs (35.0%) remained active. The clustered patients were mainly men (92.8%) who had sex with men (MSM) (81.5%), Spanish (80.6%), and young adults (median age at diagnosis of 32.6 years). They had lower percentages of late diagnosis and AIDS cases (42.1% and 13.6%, respectively), whereas the presence of recent seroconverters (31.1%), HIV-1 B subtypes (79.4%), and transmission drug resistance (20.3%) increased within TCs, with regard to not-clustered individuals. Among the TCs of non-B variants, circulating recombinant forms (CRF) were predominant (87.5%), with the highest frequencies for CRF19_cpx (17.0% of non-B subtype sequences in TCs); CRF02_AG (15.9%); and CRF01_AE (9.1%). In conclusion, over half of our cohort was included within a TC. More than a third of TCs found could be considered active transmission events. Belonging to a TC was related to MSM, Spanish origin, recent seroconversion, high prevalence of resistance mutations, and B HIV subtype. Among the non-B genetic forms in TCs, we found a high prevalence of CRF19_cpx, CRF02_AG, and CRF01_AE variants.

We evaluated the utility of Architect core antigen assay® Abbott Diagnostics (HCVAg) for monitoring patients with HCV infection and compared to HCV-RNA quantification (Cobas Ampliprep TaqMan-Roche Diagnostics). Samples from 262 patients were studied. Mean baseline HCV RNA and HCVAg levels were similar for responders (6.2 log IU/mL and 3.4 log fmol/L) and non-responders (6.1 log IU/mL and 3.2 log fmol/L), respectively. Only 10 patients failed to achieve SVR12 and all were detected by both assays. To evaluate HCVAg quantification as a tool for the detection of failure to DAAs, we performed a retrospective study of 132 non-responder patients. Mean HCV RNA and HCVAg levels at the time of detection of therapeutic failure were 5.88±0.97 log IU/mL and 3.19±0.79 log fmol/L, respectively. HCVAg (>3 fmol/L) was detected in 130/132 patients (98.5%). HCVAg assay was useful for patient selection and for evaluating virological response to DAAs in the real world.

Background and aim: undiagnosed hepatitis C virus (HCV) infection and/or inadequate access to care are barriers to the elimination of HCV. Reflex testing has proven to facilitate referral to care, treatment and viral elimination. In this study, a reflex testing program was implemented in Andalusia and its impact on access to care was evaluated. Patients and methods: an observational, retrospective and prospective study was performed across diagnostic laboratories responsible for HCV diagnosis in southern Spain. After surveying the barriers to performing reflex testing, the number of patients that were not referred for care in 2016 was retrospectively studied (pre-reflex cohort). Subsequently, several measures were proposed to overcome the identified barriers. Finally, reflex testing was implemented and its impact evaluated. Results: the pre-reflex cohort included information from 1,053 patients. Slightly more than half of the patients (n = 580; 55%) visited a specialist for treatment evaluation during a median period of 71 days (interquartile range = 35-134) since the date of diagnosis. The post-reflex cohort (September 2017 to March 2018) included 623 patients. Only 17% (n = 106) of the patients had not been referred for care or evaluated for treatment in a median period of 52 days (interquartile range = 28-86). Conclusions: in 2016, nearly half of new HCV diagnoses in southern Spain were not referred for care. Barriers to the implementation of reflex testing were overcome in our study. Moreover, this strategy was effectively implemented in 2017. Reflex testing contributed to improving referral for care. This program will contribute to the micro-elimination of hepatitis C in Spain.

[Objective] To study the prevalence and distribution of HBV genotypes in Spain for the period 2000–2016., [Methods] Retrospective study recruiting 2559 patients from 17 hospitals. Distribution of HBV genotypes, as well as sex, age, geographical origin, mode of transmission, HDV-, HIV- and/or HCV-coinfection, and treatment were recorded., [Results] 1924 chronically HBV native Spanish patients have been recruited. Median age was 54 years (IQR: 41–62), 69.6% male, 6.3% HIV-coinfected, 3.1% were HCV-coinfected, 1.7% HDV-co/superinfected. Genotype distribution was: 55.9% D, 33.5% A, 5.6% F, 0.8% G, and 1.9% other genotypes (E, B, H and C). HBV genotype A was closely associated with male sex, sexual transmission, and HIV-coinfection. In contrast, HBV genotype D was associated with female sex and vertical transmission. Different patterns of genotype distribution and diversity were found between different geographical regions. In addition, HBV epidemiological patterns are evolving in Spain, mainly because of immigration. Finally, similar overall rates of treatment success across all HBV genotypes were found., [Conclusions] We present here the most recent data on molecular epidemiology of HBV in Spain (GEHEP010 Study). This study confirms that the HBV genotype distribution in Spain varies based on age, sex, origin, HIV-coinfection, geographical regions and epidemiological groups., This study has been funded in part by the funds of the research project GEHEP-2018-010, granted by the Hepatitis Group of the Spanish Society of Infectious Diseases and Clinical Microbiology (Grupo de Hepatitis de la Sociedad Española de Enfermedades Infecciosas y Microbiología Clínica, GEHEP/SEIMC).

Integration of molecular, clinical, and demographic data represents a powerful tool to understand the dynamics of local HIV-1 transmission chains (TCs). The aim of our study was the phylogenetic analysis of the TCs within a HIV-1 cohort and the description of the relevant patient data within a TC. We performed a phylogenetic analysis of 757 sequences from newly HIV-1 diagnosed patients in Málaga (Southern Spain) during the period 2004–15. We used partial pol gene sequences in a preliminary phylogenetic reconstruction using the Neighbour Joining method (MEGA v6.06 program). After eliminating branches with bootstrap values

Background CRF19_cpx is a complex circulating recombination form (CRF) of HIV-1. We describe the characteristics of an outbreak of the CRF19_cpx variant among treatment-naive patients in southern Spain. Methods The study was undertaken at the Virgen de la Victoria Hospital, a reference centre for the analysis of HIV-1 genotype in Malaga (Spain). Subtyping was performed through REGA v3.0 and the relationship of our CRF19_cpx sequences, among themselves and regarding other reference sequences from the same variant, was defined by phylogenetic analysis. We used PhyML program to perform a reconstruction of the phylogeny by Maximum Likelihood method as well as further confirmation of the transmission clusters by Bayesian inference. Additionally, we collected demographic, clinical and immunovirological data. Results Between 2011 and 2016, we detected 57 treatment-naive patients with the CRF19_cpx variant. Of these, 55 conformed a very well-defined transmission cluster, phylogenetically close to CRF19_cpx sequences from the United Kingdom. The origin of this subtype in Malaga was dated between 2007 and 2010. Over 50% of the patients presented the non-nucleoside reverse transcriptase inhibitor G190A resistance mutation. This variant was mostly represented by young adult Spanish men who had sex with men. Almost half of them were recent seroconverters, though a similar percentage was diagnosed at a late state of HIV infection. Five cases of AIDS and one non-AIDS defined death occurred during follow-up. The majority of patients treated with first-line combination antiretroviral therapy (ART) responded. Conclusions We report the largest HIV-1 CRF19_cpx cohort of treatment-naive patients outside Cuba, almost all emerging as an outbreak in the South of Spain. Half the cases had the G190A resistance mutation. Unlike previous studies, the variant from Malaga seems less pathogenic, with few AIDS events and an excellent response to ART.

We report the largest study on the prevalence and distribution of HCV genotypes in Spain (2000-2015), and we relate them with clinical, epidemiological and virological factors. Patients from 29 hospitals in 10 autonomous communities (Andalusia, Aragon, Castilla-Leon, Catalonia, Galicia, Canary Islands, Madrid Community, Valencian Community, Murcia Region and Basque Country) have been studied. Annual distribution of HCV genotypes and subtypes, as well as gender, age, transmission route, HIV and/or HBV coinfection, and treatment details were recorded. We included 48595 chronically HCV-infected patients with the following characteristics: median age 51 years (IQR, 44-58), 67.9% male, 19.1% HIV-coinfected, 23.5% HBV-coinfected. Parenteral transmission route was the most frequent (58.7%). Genotype distribution was 66.9% GT1 (24.9% subtype 1a and 37.9% subtype 1b), 2.8% GT2, 17.3% GT3, 11.4% GT4 and 0.1% GT5 and 0.02% GT6. LiPA was the most widely HCV genotyping test used (52.4%). HCV subtype 1a and genotypes 3 and 4 were closely associated with male gender, parenteral route of infection and HIV and HBV coinfection; in contrast, subtype 1b and genotype 2 were associated with female gender, nonparenteral route and mono-infection. Age was related to genotype distribution, and different patterns of distribution and biodiversity index were observed between different geographical areas. Finally, we describe how treatment and changes in transmission routes may have affected HCV genotype prevalence and distribution patterns. We present the most recent data on molecular epidemiology of hepatitis C virus in Spain. This study confirms that genotype distributions vary with age, sex, HIV and HBV coinfection and within geographical areas and epidemiological groups.

Resumen Introduccion Las variaciones del gen C originan las mutaciones precore y las core, que influyen en la produccion de AgHBe. El fallo en los tratamientos antivirales se debe a la presencia de las variaciones en el gen P, que originan las mutaciones de la polimerasa viral. Metodo Hemos realizado estudio genotipico del VHB mediante secuenciacion del gen P, y del gen C en pacientes con hepatitis cronica por virus B durante un periodo de cinco anos. Resultados El 75 % presentaron alguna mutacion en la region precore, core o en ambas. El 37 % mostro mutaciones de resistencia al tratamiento antiviral. Los genotipos mas frecuentes fueron el A y el D. Conclusiones La presencia de mutaciones core/precore en pacientes con hepatitis cronica hace obligado un control mas estrecho de estos enfermos. La deteccion de resistencias debe hacerse lo mas rapido posible antes de que se produzca un aumento de la carga viral.

Dolutegravir (S/GSK1349572) is a second-generation HIV-1 integrase inhibitor (INI) in advanced clinical development. It has shown good antiviral activity in most patients with prior raltegravir failure, although changes at the integrase codon 148, particularly when combined with other mutations, confer reduced susceptibility and may impair dolutegravir activity. Mutations believed to be associated with dolutegravir resistance at positions 92, 101, 124, 148, 153, and 193 were assessed in patients either INI-naïve or experiencing failure to raltegravir-based regimens. The integrase coding region was sequenced using an in-house nested-PCR protocol. HIV-1 subtyping was carried out using the Stanford algorithm. A total of 638 plasma samples were analyzed from 535 INI-naïve and 103 raltegravir-experienced patients. Non-B subtypes were recognized in 20.8% patients. Mutations L101I and T124A were significantly more prevalent in patients with non-B subtypes (66.9% vs. 45.7% for L101I; 61.7% vs. 25.9% for T124A; and 39.1% vs. 12.7% for L101I+T124A; p0.001 in all cases). E92Q and Q148H/R were only seen in raltegravir-experienced patients and exclusively infected with subtype B (1.9% vs. 0%, p=0.026, for E92Q and 12.6% vs. 0%, p0.001, for Q148H/R). On the contrary, T124A was more frequent in INI-naïve than raltegravir-experienced patients (35.1% vs. 24.3%, p=0.040). S153Y/F was absent in this dataset. Polymorphic changes L101I and T124A were more frequent in HIV-1 non-B than B subtypes. T124A was more frequent in INI-naïve patients but E92Q and Q148H/R were only seen in raltegravir-experienced individuals. Thus, both HIV-1 subtype and raltegravir exposure may influence the antiviral activity of dolutegravir.

Data on occult HBV infection in HIV patients are conflicting. We aimed to analyse the prevalence and clinical significance of occult hepatitis B in HIV-infected subjects.An open-label, cross-sectional, multicentre study including all subjects with isolated anti-HBc seropositivity from a cohort of 3,030 HIV-infected patients was undertaken. HBsAg and HBsAb were both negative in all cases, and those patients with acute or convalescent hepatitis B were excluded. HBV DNA was quantified by PCR with a detection limit of 20 IU/mL.We found 5 cases (2.5%) of occult hepatitis B among 202 HIV-patients with isolated anti-HBc. The mean HBV DNA was 66 (15-112) IU/mL, none had symptomatic hepatitis, and their features, including aminotransferase levels, were similar to those without occult HBV infection.Occult hepatitis due to HBV is very unusual in HIV-positive patients with isolated anti-HBc. The use of standard regimens of HAART including drugs with activity against HBV might underestimate the prevalence of occult HBV infection. These patients had a very low viral load, no identifiable risk factors, and no greater risk of hypertransaminasaemia or the development of symptomatic hepatitis.

Introduccion La prevalencia de mutaciones primarias de resistencia varia segun los estudios. Analizamos dicha prevalencia, asi como los subtipos del virus de la inmunodeficiencia humana (VIH) en nuestra area. Metodos Estudio prospectivo en el que se realiza un test genotipico ( Trugene HIV-1 genotyping kit ; Bayer Healthcare Diagnostics) de resistencias e identificacion del subtipo de VIH a todos los pacientes diagnosticados de infeccion por VIH en la provincia de Malaga durante el ano 2005. Resultados Se diagnosticaron 172 casos, 6 de ellos seroconversores recientes. Presentaron mutaciones de resistencia el 7,8% (intervalo de confianza [IC] del 95%: 3,5; 12,0%) de los 153 pacientes en los que se pudo tener un test genotipico (6 a los inhibidores de la transcriptasa inversa no analogos de los nucleosidos [ITINAN], 4 a los inhibidores de la transcriptasa inversa analogos de los nucleosidos [ITIAN], y 3 a los inhibidores de la proteasa [IP]). El 81,8% de los pacientes tenian subtipo B del VIH y el 18,1% no B (51,8% de ellos eran subsaharianos en los que la prevalencia de este subtipo fue del 73,6%). Entre los pacientes europeos solo los espanoles presentaron subtipo no B (prevalencia del 7,7%). El unico factor que se asocio con mutaciones de resistencia fue la seroconversion ( odds ratio [OR]: 9,2; IC 95%: 1,3-61,9; p Conclusiones La prevalencia de mutaciones de resistencia en pacientes con nuevo diagnostico de infeccion por el VIH en la provincia de Malaga no es despreciable, y la seroconversion es el unico factor que se asocio a su presencia. Destaca la alta prevalencia de VIH subtipo no B en la poblacion espanola. Con estos datos se debe recomendar la realizacion de tests genotipicos de resistencia en todos los nuevos diagnosticos de nuestra area.

Background We describe the characteristics of an HIV-1 strain with six viral reverse transcriptase mutations (D67N, T69N/D, V118I, V179D, T215S and K219Q), which we have called the Malaga strain. This strain was detected in treatment-naive patients from southern Spain. Methods The study was undertaken at the Virgen de la Victoria Hospital, Malaga, a reference centre for the study of HIV-1 genotype resistance in Andalusia (the 'Costa del Sol'), Spain. Genotypic resistance testing was done in an automated sequencer. Phylogenetic analysis was performed using a 630 bp region of the reverse transcriptase with the mutations mentioned. Results Between 2007 and 2014, we detected the Malaga strain in 30 treatment-naive patients. All were MSM, seen at five hospitals on the Costa del Sol. In all cases, the HIV-1 was subtype B with viral tropism R5. Phylogenetic analysis based on the reverse transcriptase sequence showed consistent grouping (with a bootstrap value of the common node of 100%) of the isolates that shared the mutation pattern mentioned. This strain has not been detected elsewhere or in previously treated patients. All of the patients treated with first-line combination ART responded. Conclusions We report a cluster of an HIV-1 strain with multiple resistance mutations that was transmitted over a period of >8 years, affecting 30 naive patients from the same geographical area. The strain was susceptible to first-line combination ART.

Variations of C gene give rise to precore and basal core mutations, which influence HBeAg expression The antiviral treatment failure is due to the presence of variations in the gene P, which cause mutations in the viral polymerase.We performed genotyping of HBV P gene by sequencing, and gene C in patients with chronic hepatitis B over a period of five years.A total of 75% of the patients had some mutation in precore or in basal core promoter regions, and 37% demonstrated resistance mutations to antiviral treatment. The most frequent genotypes were A and D.The presence of mutations in core/precore regions in patients with chronic hepatitis has led to tighter control of these patients. Detecting for resistance should be done as quickly as possible before there is an increase in viral load.

OBJECTIVES To determine the feasibility and outcomes of long-distance interactive expert advice for treatment-experienced patients. METHODS HIV-1-infected patients on failing highly active antiretroviral therapy (HAART) were prospectively submitted for consultation by treating physicians to an expert panel using a standard e-mail form including: resistance tests, antiretroviral history, adherence, CD4 counts, HIV-1-RNA levels and HCV/HBV co-infection. Conference calls (CCs) were scheduled monthly to discuss 10 new patients. RESULTS One hundred and fifteen patients were discussed (86% male; 45% intravenous drug users). The median length of HIV infection was 10 years and subjects were treated for a median of 8 years with a median of 5.25 previous HAART regimens. Ninety per cent were triple-class experienced [nucleoside reverse transcriptase inhibitors (NRTIs)/non-NRTIs (NNRTIs)/protease inhibitors (PIs)]. Median CD4 cell count was 298 cells/mm(3) and median viral load was 19 700 copies/mL. Overall, 60% had >or=5 reverse transcriptase mutations and 67% had >or=5 protease mutations, and most patients were NNRTI-resistant. Drugs more frequently recommended by experts were: lamivudine/emtricitabine > tenofovir > abacavir > zidovudine > didanosine > stavudine (NRTIs) and tipranavir > lopinavir > atazanavir > saquinavir (PIs). Enfuvirtide was recommended in 65% of cases. Concordance between recommended and prescribed regimens was 74.7%. Virtually all discordances were due to patient refusal of complex regimens. Outcomes at 24 weeks: HIV-1-RNA

Producción Científica, Background: Human immunodeficiency virus (HIV) treatment guidelines have evolved, shifting from more-aggressive to more-conservative approaches. The potential impact of these shifts on the transmission of drug-resistant virus is unknown. Methods: Drug-resistance genotypes were examined in all consecutive patients with recent HIV type 1 (HIV-1) seroconversion (hereafter, "HIV-1 seroconverters") seen at 10 Spanish hospitals since 1997. During the same period, the proportion of patients with chronic HIV-1 infection having undetectable viremia was examined, to estimate the extent and effectiveness of antiretroviral therapy. Results: A total of 141 recent HIV-1 seroconverters were identified, 67.4% of whom were men who have sex with men. The rate of primary drug-resistance mutations, by year of infection, was 33.3% for 1997, 29.4% for 1998, 20% for 1999, 14.3% for 2000, 3.4% for 2001, 15.4% for 2002, and 10.9% for 2003. On the other hand, the proportion of 8388 persons with chronic HIV-1 carriage who had an undetectable virus load was 33.4% for 1997, 34.6% for 1998, 39.7% for 1999, 47.5% for 2000, 52.9% for 2001, 39.7% for 2002, and 58.1% for 2003. A significant inverse correlation between transmission of drug-resistant HIV-1 and undetectable virus load was found (r=-0.955, by Spearman's test; P=.001). The lowest rate of transmission of drug-resistant HIV-1 was seen in 2001, when relatively "aggressive" treatment guidelines were used. Transmission of drug-resistant HIV-1 increased in 2002, in parallel with a reduction in the number of patients with chronic HIV-1 carriage and undetectable virus load, reflecting the popularity of drug holidays or treatment interruptions. Conclusion: The rate of drug resistance in recent HIV-1 seroconverters inversely correlates with the proportion of chronically HIV-1-infected individuals who have undetectable virus loads in the same region, which indirectly reflects antiretroviral treatment rules at any given time., Redes de Investigación en SIDA ( RIS project 173)

Producción Científica, The prevalence of drug resistance mutations was 12.1% among 198 persons who experienced human immunodeficiency virus (HIV) seroconversion identified in Spain during 1997–2004. There was a significant increase of K103N and of non-B subtypes over time. Transmission of HIV infection around the time of seroconversion was shown in 8 couples and in 2 clusters of 3 individuals, Red de Investigación en SIDA (RIS- project 17)

Streptococcus pneumoniae is the most frequent cause of non-hospital acquired pneumonia and meningitis in adults, and bacterial otitis media in children. Moreover, it causes a third of all acute sinusitis cases. Penicillin has been the treatment of choice for almost 50 years. Gradually, penicillin-resistant pneumococci have appeared throughout the world. Our aim was to investigate the epidemiology, pattern of resistance and serotypes of Streptococcus pneumoniae infection in our area.Over a period of two years (May 1997-May 1999), Streptococcus pneumoniae strains were isolated in the Clinical Microbiology Unit of the University Hospital Virgen de la Victoria in Málaga, Spain. This is a 750-bed hospital covering a population of 407,480 inhabitants, and admitting 21,500 hospitalized patients per year. Streptococcus was identified by standard procedures: serotyping was done with the Quellung test and antibiotic susceptibility study by the disk diffusion method and E-test.Streptococcus pneumoniae infection was diagnosed in 170 patients during the years studied. The microorganism was isolated from samples of sputum (82), blood (43), aspirated bronchial fluid, cerebrospinal fluid (6), and exudates (7). Non-hospital origin was identified in 88% of cases. The mean hospital stay was 12 days and mortality was 12.4%. Some 45.9% of the isolated strains were resistant to penicillin and 20% to cefotaxime. We found 31 different serotypes, with 77% of the isolated strains belonging to 12 serotypes. Serotypes 19, 3 and 6B were the most frequent in non-hospital infection, whereas 9V and 23F were related with nosocomial infection. Penicillin-resistant strains of Streptococcus pneumoniae belonged to 19 different serotypes; 6B, 9V, 14, 19 and 23F were the most important.As was expected, Streptococcus pneumoniae infections of mainly non-hospital origin in our area were characterized by elevated mortality and high-level resistance to penicillin. Immunosuppression was a predisposing factor.